Antibodies specific for carcinogen-DNA adducts have probed the nature, extent and consequences of in vitro and in vivo DNA modification. Biological samples of DNA substituted with 2-acetylaminofluorene (2-AAF), benzo(a)pyrene (BP) or cis-dichlorodiammineplatinum (II) (cis-DDP) were analyzed by immunofluorescence and quantitative immunoassays able to detect 1 adduct in one hundred million nucleotides. Continuous AAF feeding resulted in a rapid accumulation of adducts (3-4 weeks) in rat liver DNA followed by a plateau (4-8 weeks.) When 2-AAF fed animals were placed on control diet, adduct removal was biphasic with a rapid initial Phase I (up to 2 wk) followed by a slow Phase II (2-4 wk). Persistent adduct accumulated slowly due to a loss of phase II removal after 2 wk of carcinogen feeding. In contrast to adduct levels observed in 2-AAF-fed liver, binding of BP to DNA of mouse skin and mouse epidermal cells in culture after exposure to either initiating or transforming doses was more than 50 fold lower. The kinetics of repair for BPdG in vivo and in vitro were biphasic (as in liver) but much more rapid, with 50% removal by 1-3 days. Thus adduct accumulation and removal seem to be specific for a particular target tissue and an individual carcinogen, and may not be quantitatively related to efficiency of tumorigenesis or transformation. Antisera specific for BPdG-DNA (bidentate N7 dideoxyguanosine adduct) have been successful in measuring specific adducts as a result of polycyclic aromatic hydrocarbon exposure in lung tissue and buccal smears from lung cancer patients and smokers, and platinum drug chemotherapy in nucleated blood cell DNA from cancer patients.